HER-dimerization inhibitors: evaluating pertuzumab in women's cancers

Importance of the field: Pertuzumab is a human EGF receptor (HER)dimerization inhibitor that represent a novel class of agents aimed at blocking HER2 from pairing with other receptors of the HER family. In this review, we discuss the background and scientific rationale, related to pertuzumab as it has undergone development for women's cancers. Areas covered in this review: Pre-clinical and clinical trials, published or presented at national meetings from 1995 to the present, are included in this review. What the reader will gain: A Phase 11 trial in HER2-positive metastatic breast cancer showed promising activity of pertuzumab when it was combined with trastuzumab and a randomized Phase III trial is now underway. Pertuzumab, when evaluated in recurrent ovarian cancer showed limited activity when combined with chemotherapy in platinum-sensitive and platinum-resistant disease. However, a recent subset analysis suggests that HER3 mRNA levels may predict response to pertuzumab in ovarian cancer. Take home message: HER-dimerization inhibitors represent a novel mechanism of inhibition of HER pathways. Pertuzumab may play a role in the management of HER2-positive breast cancer. The potential benefit of pertuzumab in ovarian cancer is unclear, but low HER3 levels may suggest a sub-group of patients that can benefit from pertuzumab